Nivolumab is part of a class of immunotherapy drugs known as PD-1 blocking antibodies. These drugs work by targeting the PDL-1 receptor — a known immunotherapy biomarker for lung and other cancers — to boost immune responses to the cancer.

Patients were randomized to receive either immunotherapy or standard-of-care chemotherapy. About 60 percent of patients treated on the trial ultimately crossed over to the immunotherapy treatment arm due to disease progression.

Results from this new study showed that nivolumab did not result in longer progression-free survival compared with chemotherapy in the overall population. The response rate for patients receiving nivolumab was 26.1 percent, with a 12.1 month median duration of response before disease progression. The response rate for patients treated on the chemotherapy arm was 33.5 percent, but median duration of response was just 5.7 months before disease progression.

“The good news is that we discovered that a subset of patients who had both high tumor mutation burden and high PDL-1 positive status did experience a significant benefit from immunotherapy,” says Carbone.

Patients with both high tumor mutation burden and high PDL-1 positive status had a 75 percent response rate compared with a 16 percent response rate to immunotherapy among patients with low mutation burden and low PDL-1. These same two groups had 25 percent and 23 percent response rates, respectively, when treated with chemotherapy, showing that these markers were selective for immunotherapy.

Understanding a patient’s overall tumor burden through genomic testing, says Carbone, could help identify patients most likely to benefit from immunotherapy before therapy ever begins.

“This study is an important step toward understanding the impact of tumor mutation burden and PDL-1 in immunotherapy response. This data shows we should evaluate these two factors independently to most accurately define who will benefit from immunotherapy,” says Carbone.

The findings are reported in the June 22, 2017, issue of the New England Journal of Medicine.